Optimal oral anticoagulant therapy in patients with mechanical heart valves

N Engl J Med. 1995 Jul 6;333(1):11-7. doi: 10.1056/NEJM199507063330103.


Background: The optimal intensity of oral anticoagulant therapy for patients with mechanical heart valves (i.e., the level at which thromboembolic complications are effectively prevented without excessive bleeding) is not known. We attempted to determine the optimal intensity by calculating the incidence of both complications at different levels of anticoagulation.

Methods: Data were collected on all patients with mechanical heart valves who have been seen at four regional Dutch anticoagulation clinics since 1985. The primary outcome events were episodes of thromboembolism or major bleeding. The intensity-specific incidence of each type of event was calculated as the number of events that occurred at a certain intensity of anticoagulation (expressed in terms of the international normalized ratio [INR]) divided by the number of patient-years during which the INR was at this level in the total patient population.

Results: A total of 1608 patients were followed during 6475 patient-years. Cerebral embolism occurred in 43 patients (0.68 per 100 patient-years) and peripheral embolism in 2 (0.03 per 100 patient-years). Intracranial and spinal bleeding occurred in 36 patients (0.57 per 100 patient-years) and major extracranial bleeding in 128 (2.1 per 100 patient-years). The optimal intensity of anticoagulation, at which the incidence of both complications was lowest, was achieved when the INR was between 2.5 and 4.9.

Conclusions: The intensity of anticoagulant therapy for patients with prosthetic heart valves is optimal when the INR is between 2.5 and 4.9. To achieve this level of anticoagulation, a target INR of 3.0 to 4.0 is recommended.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acenocoumarol / administration & dosage*
  • Acenocoumarol / adverse effects
  • Aged
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Heart Valve Prosthesis*
  • Hemorrhage / chemically induced*
  • Hemorrhage / epidemiology
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Phenprocoumon / administration & dosage*
  • Phenprocoumon / adverse effects
  • Prothrombin Time
  • Thromboembolism / epidemiology
  • Thromboembolism / prevention & control*


  • Acenocoumarol
  • Phenprocoumon